90 articles - From Friday Jun 17 2022 to Friday Jun 24 2022
Guidelines, position statements, white papers, technical reviews, consensus statements, etc…
| CA Cancer J Clin |
meta-analyses and systematic reviews
| Blood Adv |
| Thromb Haemost |
Systematic Review and Meta-Analysis of Thromboprophylaxis with Heparins Following Intracerebral Hemorrhage. Thromboprophylaxis was effective in preventing DVT and PE without increasing the risk of hematoma expansion or bleeding among ICH patients. Future studies should explore the long-term effects of thromboprophylaxis in this population, particularly on the functional outcomes. |
RCT, clinical trials, retrospective studies, etc…
| Am J Hematol |
A genomic-augmented multivariate prognostic model for the survival of Natural-killer/T-cell lymphoma patients from an international cohort. When we assign an additional risk-score to samples, which are mutant for the GPM, the Harrell's C-indices of GPM-augmented IPI, PINK and PINK-E improved significantly (P<0.001, |
Chromosome 1q21 Aberrations Identify Ultra High-Risk Myeloma with Prognostic and Clinical Implications. We further validated our findings in an independent cohort of 272 patients. In conclusion, presence of +1q21 is associated with more advanced disease, inferior PFS and OS but especially patients with R-ISS-3 disease and +1q21 have a very poor outcome comprising an ultra-high-risk group. |
Impact of Autologous Hematopoietic Cell Transplantation on Disease Burden Quantified by Next-Generation Sequencing in Multiple Myeloma Treated with Quadruplet Therapy. Forty per cent achieved MRD reduction in MRD burden with AHCT. Serial NGS MRD demonstrates the incremental effect of AHCT in MM marrow burden in the context of quadruplet induction, particularly in high risk MM. |
Predictors of hematologic response and survival with stem cell transplantation in AL amyloidosis: a 25-year longitudinal study. The 100-day treatment-related mortality rate was 3% in the latest treatment period (2012-2021), and the 25-year risk of t-MDS/AML was 3%. We conclude that HDM/SCT induces durable hematologic responses and prolonged survival with improved safety in selected patients with AL amyloidosis. |
| Ann Oncol |
Oncology clinical trial disruption during the COVID-19 pandemic: a COVID-19 and cancer outcomes study. Substantial disruptions in clinical trial activities were observed early during the pandemic, with a gradual recovery during ensuing time periods, both from an enrollment and an activation standpoint. The observed decline was more prominent among academically sponsored trials, and racial disparities were seen among people taken off trial. |
Single-agent anti-PD-1 or combined with ipilimumab in patients with mucosal melanoma: an international, retrospective, cohort study. MM has poor prognosis. Treatment efficacy of anti-PD1+/-ipilimumab was similar and did not differ by ethnicity/race. Naso-oral primaries had numerically higher response to anti-PD1/ipilimumab, without difference in survival. The addition of ipilimumab did not show greater benefit over anti-PD1 for other primary sites. In responders, mDOR was short and acquired resistance was common. Other factors, including site and number of metastases were associated with survival. |
| Blood |
Aberrant EVI1 splicing contributes to EVI1-rearranged leukemia. The mutant SF3B1 spliceosome depends upon an exonic splicing enhancer within EVI1 exon 13 to promote usage of a cryptic branch point and aberrant 3' splice site within intron 12 resulting in the generation of this isoform. These data provide a mechanistic basis for the frequent co-occurrence of SF3B1 mutations as well as new insights into the pathogenesis of myeloid leukemias harboring inv(3)/t(3; 3). |
Deregulation and epigenetic modification of BCL2-family genes cause resistance to venetoclax in hematologic malignancies. A compound screen revealed TRAIL-mediated apoptosis as a target to overcome BAX deficiency. Furthermore, antibody or CAR T cells eliminated venetoclax resistant lymphoma cells, paving a clinically applicable way to overcome venetoclax resistance. |
Enasidenib vs conventional care in mutant-IDH2 relapsed/refractory acute myeloidleukemia: a randomized, phase 3 trial. The primary study endpoint was not met but OS was confounded by early dropout and subsequent AML-directed therapies. Enasidenib provided meaningful benefits in EFS, TTF, ORR, HI, and RBC-TI in this heavily pretreated older mutant-IDH2 R/R AML population. |
Liver to lung microembolic NETs promote Gasdermin-D-dependent inflammatory lung injury in Sickle Cell Disease. Remarkably, these NETs travel intravascularly from liver to lung, where they promote neutrophil-platelet aggregation and the development of acute lung injury. This study introduces a novel paradigm that liver to lung embolic translocation of NETs promotes pulmonary vascular vaso-occlusion, and identifies a new GSDMD-mediated, P-selectin-independent mechanism of lung injury in SCD. |
Macaque Clonal Hematopoiesis Model Demonstrates Expansion of TET2-Disrupted Clones and Utility for Testing Interventions. The model was used to test the impact of IL-6 blockage by tocilizumab, documenting a slowing of TET2 mutated expansion, suggesting that interruption of the IL-6 axis may remove the selective advantage of mutant HSPCs. These findings provide a model for examining the pathophysiology of CH and give insights into potential therapeutic interventions. |
Single-cell multiomics reveal the scale of multi-layered adaptations enabling CLL relapse during venetoclax therapy. Our studies reveal the extent of plasticity of CLL cells in their ability to evade venetoclax-induced apoptosis. Importantly, these findings pinpoint new approaches to circumvent venetoclax resistance and provide a specific biological justification for the strategy of venetoclax discontinuation once maximal response is achieved rather than maintaining long-term selective pressure with the drug. |
Specification of hematopoietic stem cells in mammalian embryos: A rare or frequent event? Here, we explore recent advances in understanding the numbers and kinetics of cells that emerge during development to support lifelong hematopoiesis-advances that are made possible by new technologies allowing interrogation of lifelong blood potential without embryo perturbation or transplantation. Illuminating the dynamics of these cells during normal development informs efforts to better understand the origins of hematologic disease and engineer HSCs from differentiating pluripotent stem cells. |
TET2-mutant clonal hematopoiesis and risk of gout. These studies show that TET2-mutant CHIP is associated with an increased risk of gout in humans and that MSU crystals lead to elevated IL-1B levels in Tet2 knockout murine models. We identify CHIP as an amplifier of NLRP3-dependent inflammatory responses to MSU crystals in gout patients. |
The oral ferroportin inhibitor vamifeport improved hemodynamics in a mouse model of sickle cell disease. Accordingly, intravital video microscopy of fluorescently labeled blood cells in the microvasculature of Townes mice treated with vamifeport demonstrated diminished adhesion to the endothelium and improved hemodynamics. These preclinical data provide a strong proof-of-concept for vamifeport in the Townes model of SCD and support further development of this compound as a potential novel therapy in SCD. |
| Blood Adv |
Anchoring IgG-degrading enzymes to the surface of platelets selectively neutralizes antiplatelet antibodies. Treatment of mice expressing human Fc |
CD58 loss in tumor cells confers functional impairment of CAR T cells. We found that disruption of CD58 in tumor cells induced the formation of suboptimal immunological synapse (IS) with CAR T cells, which conferred functional impairment of CAR T cells, including the attenuation of cell expansion, degranulation, cytokine secretion and cytotoxicity. In summary, we describe a potential mechanism of tumor intrinsic resistance to CAR T-cell therapy and suggest that this mechanism may be leveraged for developing therapeutic strategies to overcome resistance to CAR T-cell therapy in B-cell malignancies. |
CPT2 K79 Acetylation Regulates Platelet Lifespan. Blocking LCACs generation with the inhibitors of AMPK or CPT1, the agonists of Sirt3, and antioxidants tremendously retarded platelet storage lesion in vitro and prolong the survival of stored platelets in vivo post transfusion by single or combined use. In short, we discovered that CPT2 acetylation attenuates fatty acid oxidation and exacerbates platelet storage lesion and may serve as a new target for improving platelet storage quality. |
D-Dimer and Risk for Thrombosis in Adults with Newly Diagnosed Acute Lymphoblastic Leukemia. In conclusion, D-dimer levels at ALL diagnosis are associated with venous or arterial thrombosis at 100 days. Future studies should include D-dimer collated with other known risk factors to build a risk assessment model for thrombosis in patients with newly diagnosed ALL. |
Improvements in allogeneic hematopoietic cell transplantation outcomes for adults with ALL over the past 3 decades. Allo-HCT outcomes for adults with ALL have improved over the past 30 years. Improved outcomes in the future will require more effective prevention of relapse in patients with ALL not in CR1 and in those with high-risk chromosomal abnormalities. |
Metabolic reprogramming under hypoxic storage preserves faster oxygen unloading from stored red blood cells. Correlations between gas-handling and lipidomic changes were modest. Thus, hypoxic storage of RBCs preserves key metabolic pathways and O2 exchange properties, thereby improving the functional quality of blood products and potentially influencing transfusion outcomes. |
Non-canonical Sonic Hedgehog signaling amplifies platelet reactivity and thrombogenicity. In consistence, inhibition of Shh pathway significantly impaired arterial thrombosis in mice. Taken together, above observations strongly support a feed-forward loop of platelet stimulation triggered locally by Shh, similar to ADP and thromboxane A2, that contributes significantly to stability of occlusive arterial thrombus and that can be investigated as potential therapeutic target in thrombotic disorders. |
Outcomes and molecular profile of oligomonocytic CMML support its consideration as the first stage in the CMML continuum. These variables were also detected as independent adverse prognostic factors for OS in OM-CMML. These data support the consideration of OM-CMML as the first evolutionary stage within the proliferative continuum of CMML. |
Outcomes of elderly diffuse large B-cell lymphoma patients treated with R-CHOP: 10-year follow-up of the LNH03-6B trial. Progression/relapse led to poor prognosis after second-line chemotherapy in the pre-CAR-T era. Novel approaches in first-line and alternative treatments in second-line treatments are warranted in this population. |
Phase 2 trial of ixazomib, cyclophosphamide, and dexamethasone for previously untreated light chain amyloidosis. Given the favorable toxicity profile, an important advantage for the typically frail AL population, further evaluation of the ixazomib in other combinations in the upfront setting is warranted. This trial is registered at as NCT01864018. |
Real-world characteristics of T-cell apheresis and clinical response to tisagenlecleucel in B-cell lymphoma. In multivariate analysis, CD8 TN/SCM proportion and International Prognostic Index (IPI) at the time of apheresis were independent risk factors for early progression. Our data show that an easy characterization by flow cytometry of the T-cell phenotype at the time of decision to use commercial CAR-T cells can help to better select patients who will respond. |
Romiplostim addition to conditioning prior to HSCT allows chemotherapy reduction while maintaining engraftment levels. We thus tested if the addition of Romiplostim to the clinically applied conditioning chemotherapy regimen cyclophosphamide and busulfan leads to increased efficacy of the chemotherapeutic regimen. We found that Romiplostim not only sensitizes HSCs to chemotherapy but also enables a reduction of the main chemotherapeutic component Busulfan by half, while HSC engraftment levels are maintained in long-term, serial transplantation assays. |
Traumatic vessel injuries initiating hemostasis generate high shear conditions. This phenomenon could be explained by the low hydrodynamic resistance of the injuries as compared to that of the downstream vessel network. These findings show that high shear rates are relevant to hemostasis and not exclusive to arterial thrombosis. |
| CA Cancer J Clin |
| Haematologica |
Immune thrombocytopenia (ITP): diagnosis including secondary ITP, and selection of second line treatment Finally, there is a short section on refractory disease drawn from our extensive review in Blood in February 2020(1). The clinical nature of the discussions replete with figures and tables and with interspersion of pearls regarding efficacy and toxicity at different ages and genders, will serve the reader in management of "typical" adult patients who develop persistent and chronic ITP. |
Impaired immunosuppressive role of myeloid-derived suppressor cells in acquired aplastic anemia. These findings reveal that impaired MDSCs are involved in the immunopathogenesis of AA. Pharmacologically targeting of MDSCs by rapamycin might provide a promising therapeutic strategy for AA. |
In-depth characterization of intratumoral heterogeneity in refractory B-cell non-Hodgkin lymphoma through the lens of a Research Autopsy Program. Lastly, we show that ctDNA is suitable for the detection of ancestral mutations but may miss a significant proportion of private mutations that can be detected in tissue. Our study clearly shows the existence of intricate patterns of regional and anatomical evolution that can only be disentangled through multi-regional tumor tissue profiling. |
Monomorphic epitheliotropic intestinal T-cell lymphoma comprises morphologic and genomic heterogeneity impacting outcome. Multivariate analysis found a strong negative impact on outcome of MYC expression, TP53 mutation, STAT5B mutation and poor performance status while aberrant B-cell marker expression (20% of cases) correlated with better survival. In conclusion, MEITL is an aggressive disease with resistance to conventional therapy, predominantly characterized by driver gene alterations deregulating histone methylation and JAK/STAT signalling and encompasses genetic and morphologic variants associated with very high clinical risk. |
Prediction of complete remission and survival in acute myeloid leukemia using supervised machine learning. We demonstrate the feasibility of ML for risk stratification in AML as a model disease for hematologic neoplasms using a scalable and reusable ML framework. Our study illustrates the clinical applicability of ML as a decision support system in hematology. |
STAT5 does not drive steroid resistance in T-cell acute lymphoblastic leukemia despite the activation of BCL2 and BCLXL following glucocorticoid treatment. This explains why isolated STAT5 activation does not directly impair the steroid response. Our study suggests that STAT5 activation only contributes to steroid resistance in combination with cellular defects or alternative signaling routes that disable the pro-apoptotic and steroid-induced BIM response. |
| Thromb Haemost |
DNA Methylation and Ischemic Stroke Risk: An Epigenome-Wide Association Study. Specific DNA methylation pattern is causally associated with IS risk. These results could be useful for specifically predicting stroke occurrence and could potentially be evaluated as therapeutic targets. |
N-Glycosylation Deficiency Reduces the Activation of Protein C and Disrupts the Endothelial Barrier Integrity. However, pretreatment of cells with APC before thrombin simulation was still associated with a barrier-protecting effect. Taken as a whole, our results show that the partial loss of PMM2 in hCMEC/D3 cells is associated with impaired activation of protein C and a relative increase in barrier permeability. |
Risk Factors of Cardiovascular Death after Venous Thromboembolism: Results from a Prospective Cohort Study. Risk factors of CVDT after VTE include some traditional cardiovascular risk factors and other risk factors that are related to characteristics of VTE, and patients' comorbidities. |
Plenty of the editorials are available as full text through the publisher website using the provided link
| Blood |
| CA Cancer J Clin |
Examining the interrelationships between mindfulness-based interventions, depression, inflammation, and cancer survival. There are limited data on the long-term effects of mindfulness on depression and inflammatory markers in patients with cancer, and there are potential barriers to the implementation of mindfulness-based interventions as part of a comprehensive treatment plan. Therefore, it is necessary to further explore these questions through longitudinal studies to establish a survival correlation. |
| Leukemia |
The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Lymphoid Neoplasms. Besides listing the entities of the classification, we highlight and explain changes from the revised 4 th edition. These include reorganization of entities by a hierarchical system as is adopted throughout the 5 th edition of the WHO classification of tumours of al organ systems, modification of nomenclature for some entities, revision of diagnostic criteria or subtypes, deletion of certain entities, and introduction of new entities, as well as inclusion of tumour-like lesions, mesenchymal lesions specific to lymph node and spleen, and germline predisposition syndromes associated with the lymphoid neoplasms. |
The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Myeloid and Histiocytic/Dendritic Neoplasms. While a genetic basis for defining diseases is sought where possible, the classification strives to keep practical worldwide applicability in perspective. The result is an enhanced, contemporary, evidence-based classification of myeloid and histiocytic/dendritic neoplasms, rooted in molecular biology and an organizational structure that permits future scalability as new discoveries continue to inexorably inform future editions. |
Tipping the balance: toward rational combination therapies to overcome venetoclax resistance in mantle cell lymphoma. In addition, deregulation of the B-cell lymphoma-2 (BCL-2) family proteins BCL-2, B-cell lymphoma-extra large (BCL-X or MCL-1, and the recent (clinical) progress in the development of inhibitors for these BCL-2 family members, followed by the transcriptional and (post-)translational (dys)regulation of the BCL-2 family proteins, including the role of the lymphoid organ microenvironment. Based upon these insights, we discuss how rational combinations of venetoclax with other therapies can be exploited to prevent or overcome venetoclax resistance and improve MCL patient outcome. |
Letters to the editors and authors’ replies
| Am J Hematol |
| Ann Oncol |
| J Hematol Oncol |
Immune response to vaccination against SARS-CoV-2 in hematopoietic stem cell transplantation and CAR T-cell therapy recipients. In addition, seroconversion was significantly higher in patients with BCMA-based CAR-T than those with CD19-based CAR-T. Thus, an adapted vaccination strategy for HSCT and CAR-T recipients may be required, and further research on the effect of a booster dose of COVID-19 vaccine and the role of cellular response after vaccination is warranted. |
The regulation of insulin receptor/insulin-like growth factor 1 receptor ratio, an important factor for breast cancer prognosis, by TRIP-Br1. TRIP-Br1-mediated higher IR/IGF1R ratio enhanced the proliferation and survival of breast cancer cells. In conclusion, current study may provide an important information in the regulatory mechanism of how breast cancer cells have acquired higher IR/IGF1R ratio. |
all remaining publications eg case reports, images of the month, etc…
| Am J Hematol |
| Blood |
| Blood Adv |
| Haematologica |
| Lancet Haematol |
| Leukemia |